NMR spectroscopy has been used for many years in the identification of compounds by comparing the spectra of known compounds with those of the compounds to be analyzed. Various techniques employed in this method of spectral analysis are described in the literature, and NMR spectrometers are commercially available. An early description of NMR spectroscopy is provided in U.S. Pat. No. 2,561,490 to Varian.
Generally, in the operation of an NMR spectrometer, a sample to be analyzed is positioned between the pole faces of a direct current electromagnet. Conventional NMR spectroscopy is carried out by applying a short radiofrequency pulse to the sample. A receiver coil obtains a responsive signal from the sample in the form of an induced voltage. The signal then decays over time (known as Free Induction Decay (FID), typically complete after tens of milliseconds in solids). After this voltage change is amplified and detected, the NMR spectrum (a pattern of intensity as a function of frequency), is produced. Interpretation of the resulting spectra makes it possible to determine the nuclei present in molecules and their relations to the remainder of the molecule. It is necessary to wait an interval for spin-lattice relaxation to restore the Boltzmann population difference between the spin levels in the sample back to equilibrium, in order for the spins to produce a new induced voltage signal that can then be added to previous signals. The time constant (T1) characterizing this process depends upon many factors, but in solids, especially at low temperatures where sensitivity per single scan improves significantly, it can take many seconds, minutes, or even hours.
One method that has been used in NMR to decrease T1 is to add small amounts of paramagnetic ions or reagents (e.g., radicals) that contain unpaired electron spins to the sample, which are known to reduce T1. This method, Paramagnetic Relaxation Enhancement (PRE), suffers from the fact that the NMR spectrum from nuclei near the electron spins is broadened by the electron spins, limiting the useful concentration of relaxation agents that can be employed, and consequently the magnitude of the T1 reduction and/or the achievable resolution.
NMR methods that increase the sensitivity of detection in bulk (i.e., not nanoscopic) samples fall under the general term “hyperpolarization.” These involve creating population differences between nuclear spin Zeeman levels that are larger than the equilibrium Boltzmann population difference at the sample temperature. The methods may involve optical excitation (“optical pumping,” typically of semiconductors at cryogenic temperatures) or microwave irradiation to saturate Electron Paramagnetic Resonance (EPR) transitions of permanently present paramagnetic species in a process known as Dynamic Nuclear Polarization (DNP). Significant hyperpolarization by DNP from transient paramagnetic species created by photoexcitation in single crystals of doped pentacene containing a UV-absorbing molecule has been demonstrated, but the sensitivity improvement is restricted to observing NMR signals from that single molecular crystal alone.
Other hyperpolarization methods require chemical reactions to occur, or transport of hyperpolarized molecules to the NMR spectrometer. The only method that has been used to improve NMR sensitivity by simply reducing spin-lattice relaxation times T1 in solid samples is to add permanent paramagnetic species, which ultimately decreases resolution.
The interaction of unpaired electron spins with nuclear spins has played an important role in magnetic resonance spectroscopies since the earliest days of both NMR and Electron Paramagnetic Resonance (EPR) spectroscopy. The motivations for observing and interpreting such interactions vary widely. They range from obtaining atomistic information about electronic structure and delocalization of electrons (e.g. ENDOR hyperfine couplings, NMR Knight shifts, NMR contact shifts paramagnetic metal complexes), to gaining chemical structure information from distances obtained from electron-nuclear dipolar couplings, to improving the detection sensitivity of NMR by incorporating paramagnetic dopants.
With respect to improving detection sensitivity of NMR, there are two separate areas. The first area is the long-recognized ability of dopants such as transition metal ions to dramatically shorten the spin-lattice relaxation times T1 of nuclei in solids via spin-diffusion, permitting more rapid data acquisition. PRE has been useful at ambient temperature in both solution NMR as well as solid-state NMR of proteins. The effects of electron spins in paramagnetic complexes as agents of rapid spin-lattice relaxation of the nuclear spins have been analyzed, revealing that in addition to the usual ‘S-mechanism’ an additional ‘x-mechanism’ arising from the thermal average of the electron spin polarization could significantly contribute to relaxation in tumbling paramagnetic molecules. The second area is the application of paramagnetic agents to increase the nuclear spin polarization with Dynamic Nuclear Polarization (DNP), by incorporating organic radicals and biradicals into samples and using microwave irradiation of the EPR transitions at temperatures of 100 K or lower.
The interaction of light with matter affects nuclear spins only indirectly, via electronic excitations that directly alter the electron spin states. The indirect effects of light upon nuclear spins can have important consequences in solids in such areas as Optically Pumped NMR (OPNMR) of semiconductors and NV-centers in diamond, and in photo-Chemically Induced DNP (photo-CIDNP) in photosynthetic reaction centers. For specific organic molecular crystals doped with absorbers and at low temperature, photoexcited triplet states can be created and used during their short lifetime as a source for DNP polarization via microwaves (MIONP, Microwave-Induced Optical Nuclear Polarization).
The aim of these NMR approaches involving irradiation with light is to achieve increased NMR sensitivity by greatly increasing the nuclear Zeeman spin level population differences beyond the Boltzmann level. Irradiation with light has also been observed to reduce nuclear T1 values in specialized systems.
However, the broader goal of improving NMR detection sensitivity without degrading resolution remains unrealized.